Most cancer immunotherapies are conducted by administering a peptide vaccine as a cancer antigen. For increased efficacy, co-administration of a cancer antigen with an adjuvant that activates dendritic cells has been proposed. The present inventors have advanced research on adjuvants for cancer immunotherapies, and found that measles viral diRNA (defective interference RNA) functions as an adjuvant. In particular, the inventors have found that the diRNA induces IFN-β expression in human cells and enhances NK activity of NK cells, and that the diRNA administered together with a cancer antigen epitope induces marked tumor regression effect in cancer-bearing mice prepared by implanting B16 melanoma cells (Patent Literature 1). The inventors have also identified an oligo DNA that inhibits poly(I:C)-induced TLR3-mediated IFN-β expression, and reported that the oligo DNA shares the uptake receptor with poly(I:C) and the oligo DNA taken up in cells partially colocalized with TLR3 (Non Patent Literature 1). The inventors have designed a new nucleic acid based on the oligo DNA described in Non Patent Literature 1 and the diRNA described in Patent Literature 1, and discovered that the nucleic acid reaches endosomal TLR3 and exhibits potent adjuvant activity (Patent Literature 2).
Nucleic acids with adjuvant activity supplied as pharmaceuticals must comply with the GMP standard, and are hence required to be prepared by chemical synthesis. However, chemical synthetic techniques for long RNAs, such as those longer than 100 mer, have not yet been established, and such RNAs are synthesized solely by in vitro transcription. Under these circumstances, development of a chemically synthesizable nucleic acid with potent adjuvant activity and high safety has been greatly desired to provide an adjuvant formulation as a pharmaceutical for humans.